The invention relates generally to the field of chemical synthesizers. More particularly, the invention provides devices, systems and methods for synthesizing various diverse chemical products onto solid supports, such as beads, cleaving the synthesized compounds from the beads and preparing samples for analysis.
Diverse chemical products find a wide variety of uses, such as in drug discovery, genetic studies and the like. Exemplary diverse chemical products that are useful in scientific studies include peptides, oligonucleotides and other related materials.
The creation and analysis of diverse chemical products typically proceeds by synthesizing diverse collections of molecules onto a plurality of solid supports, such as beads, as is well known in the art (see, for example, "The Combinatorial Chemistry Catalog" (March 1998), available from NovaBiochem Corp., La Jolla, Calif., incorporated herein by reference). For many applications, it is desirable to simultaneously synthesize a wide variety of compounds onto the beads in a high throughput mode. In this manner, numerous compounds may be simultaneously synthesized in a single process, commonly referred to as parallel synthesis. To do so, a variety of synthesizers and techniques have been proposed, such as, for example, those described in U.S. Pat. No. 5,639,603, issued Jun. 17, 1997, and U.S. patent application Ser. No. 08/722,657, filed Sep. 27, 1996, now U.S. Pat. No. 5,866,342 the disclosures of which are herein incorporated by reference.
During the process of synthesis, the beads (which are typically held within a well or reaction vessel) are exposed to various liquids. For example, a typical process proceeds by exposing the beads to various reagents. Following this step, the beads are washed several times with a washing solution. After the compounds have been synthesized, the compounds are optionally cleaved from the beads, organized into samples and analyzed. Following cleavage, the removed compounds must then be organized into sample wells for analysis.
If is often preferable to transfer the cleaved compounds into the wells standard sized microtiter plates because such plates may then be used with most commercially available handling and processing equipment. For example, most automated plate readers, some speed vacuum concentrators, autosamplers, robotics liquid handling equipment, and the like require the samples to be placed into standard sized microtiter plates. However, the time and labor required to manually place samples into such plates can be extensive and considerably slow the process.
Another important aspect of the synthesis process is the temperature of the reagents during their exposure to the beads. For example, in some cases it will be desirable to synthesize the compounds at controlled temperatures which are well above or well below room temperature. It may also be desirable in some cases to vary the temperature of the reagents in a controlled manner during synthesis.
Exemplary synthesizers which have been developed to address such problems are described in copending application Ser. Nos. 08/736,317, filed Oct. 23, 1996, and 08/947,476, filed Oct. 10, 1997, the complete disclosures of which are herein incorporated by reference. Such types of chemical synthesizers have proven to be generally successful in synthesizing chemicals in a controlled environment. Even so, it would be desirable to provide various improvements to increase the versatility and efficiency of the synthesizers.
Hence, an object of the present invention is to provide an improved chemical synthesizer, peripheral equipment and methods for their use. In this way, the ability of produce large combinatorial collections of compounds will be greatly facilitated.